Maternal smoking during pregnancy (MSDP) has been linked to significantly increased risk for offspring smoking uptake. Given high societal costs of smoking, and risk for transgenerational transmission of offspring smoking, elucidating mechanisms underlying the MSDP-offspring smoking link is critical for intervention and prevention efforts. Acknowledging the possibility that confounding factors (e.g., genetic influences, maternal psychiatric comorbidities) may also underlie the MSDP-offspring smoking link, we follow up on one potential mechanism shown previously by Kandel and Udry l to influence smoking uptake in offspring of smoking mothers. In the only study to examine mechanisms underlying the MSDP-offspring smoking link, Kandel and Udry found that increased maternal testosterone levels during pregnancy were associated with increased risk for smoking uptake in female offspring. In the proposed study, we have an unprecedented opportunity to expand on Kandel and Udry's findings by examining two maternal hormones (testosterone and cortisol) during pregnancy as mediators of links between MSDP and offspring symptoms of nicotine dependence in both males and females using offspring from the Providence Cohort of the National Collaborative Perinatal Project (NCPP). Six hundred ninety-three adult offspring from the Providence cohort of the NCPP will be included in the study. Maternal smoking was previously assessed prospectively as part of the original NCPP battery. Symptoms of nicotine dependence in offspring were also assessed through a follow-up study of the original NCPP cohort. Maternal sera from three trimesters of pregnancy are accessible through collaboration with NIH personnel. Funding for this proposal will allow us to assay maternal sera for testosterone (and its binding protein) and cortisol (and its binding protein) as well as cotinine (a nicotine metabolite). A series of regression analyses will then be utilized to test our hypotheses regarding maternal levels of free testosterone and free cortisol as mediators of links between MSDP and offspring symptoms of nicotine dependence (measured by self-report and maternal cotinine levels) in both males and females. Identification of mechanisms underlying the MSDP-offspring smoking link may lead to targeted intervention and prevention efforts in pregnant smokers and high-risk offspring. Further, elucidating mechanisms underlying the MSDPoffspring smoking link will also represent a first step toward preventing the transmission of MSDP. [unreadable] [unreadable]